MAP2K2 (mitogen-activated protein kinase kinase 2)

Gene

• Entrez ID: 5605
• Gene name: Mitogen-activated protein kinase kinase 2
• Gene symbol: MAP2K2
• Synonyms: CFC4, MAPKK2, MEK2, MKK2, PRKMK2
• Chromosome: 19
• Chromosome location: 19p13.3
• Summary: The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase is known to play a critical role in mitogen growth factor signal transduction. It phosphorylates and thus activates MAPK1/ERK2 and MAPK2/ERK3. The activation of this kinase itself is dependent on the Ser/Thr phosphorylation by MAP kinase kinase kinases. Mutations in this gene cause cardiofaciocutaneous syndrome (CFC syndrome), a disease characterized by heart defects, cognitive disability, and distinctive facial features similar to those found in Noonan syndrome. The inhibition or degradation of this kinase is also found to be involved in the pathogenesis of Yersinia and anthrax. A pseudogene, which is located on chromosome 7, has been identified for this gene. [provided by RefSeq, Jul 2008]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs117945277	G>A,C	Likely-benign, conflicting-interpretations-of-pathogenicity, uncertain-significance	Coding sequence variant, genic downstream transcript variant, missense variant
rs121434497	A>C,T	Pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs121434498	A>C,G,T	Uncertain-significance, pathogenic, likely-pathogenic	Coding sequence variant, missense variant
rs121434499	A>G	Pathogenic-likely-pathogenic, pathogenic, likely-pathogenic	Coding sequence variant, missense variant
rs139404261	G>A	Likely-benign, conflicting-interpretations-of-pathogenicity, benign	Synonymous variant, coding sequence variant
rs267607230	G>A,C,T	Pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs387906800	C>T	Likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs539611844	G>A,T	Conflicting-interpretations-of-pathogenicity	Intron variant
rs727504370	T>C	Likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs727504382	C>T	Likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs727504836	G>A	Conflicting-interpretations-of-pathogenicity, likely-benign	Intron variant
rs730880511	C>A,T	Likely-pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs730880517	T>C	Likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs730880518	C>A	Likely-pathogenic	Coding sequence variant, missense variant
rs730880522	C>T	Likely-pathogenic	Downstream transcript variant, genic downstream transcript variant, missense variant, coding sequence variant, intron variant
rs759061964	T>C	Conflicting-interpretations-of-pathogenicity, likely-benign	Coding sequence variant, missense variant
rs763424788	G>A	Conflicting-interpretations-of-pathogenicity, likely-benign	Downstream transcript variant, intron variant, genic downstream transcript variant
rs763469132	TTC>-	Conflicting-interpretations-of-pathogenicity	Downstream transcript variant, coding sequence variant, inframe deletion, genic downstream transcript variant, intron variant
rs886041310	T>A,G	Likely-pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs1057519806	T>C,G	Pathogenic, likely-pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs1057519807	A>T	Likely-pathogenic	Coding sequence variant, missense variant
rs1057519808	T>G	Likely-pathogenic	Coding sequence variant, missense variant
rs1057519809	G>A,C	Likely-pathogenic	Coding sequence variant, missense variant
rs1057519810	C>A,T	Likely-pathogenic	Coding sequence variant, missense variant
rs1057519910	A>C,T	Pathogenic, likely-pathogenic	Coding sequence variant, missense variant
rs1114167351	ATC>-	Pathogenic	Coding sequence variant, inframe deletion
rs1135401787	A>C,G	Likely-pathogenic	Coding sequence variant, missense variant
rs1599307313	ACCTTG>-	Likely-pathogenic	Coding sequence variant, inframe deletion

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT025900	hsa-miR-7-5p	Microarray	19073608
MIRT032459	hsa-let-7b-5p	Proteomics	18668040
MIRT531850	hsa-miR-6855-5p	PAR-CLIP	22012620
MIRT531851	hsa-miR-3170	PAR-CLIP	22012620
MIRT531852	hsa-miR-3649	PAR-CLIP	22012620
MIRT531853	hsa-miR-193b-5p	PAR-CLIP	22012620
MIRT531854	hsa-miR-5589-5p	PAR-CLIP	22012620
MIRT531855	hsa-miR-492	PAR-CLIP	22012620
MIRT531856	hsa-miR-4731-5p	PAR-CLIP	22012620
MIRT531857	hsa-miR-7155-5p	PAR-CLIP	22012620
MIRT531858	hsa-miR-3692-5p	PAR-CLIP	22012620
MIRT531859	hsa-miR-196b-3p	PAR-CLIP	22012620
MIRT531860	hsa-miR-6893-3p	PAR-CLIP	22012620
MIRT531861	hsa-miR-370-3p	PAR-CLIP	22012620
MIRT639731	hsa-miR-7856-5p	HITS-CLIP	23824327
MIRT639732	hsa-miR-6864-3p	HITS-CLIP	23824327
MIRT639733	hsa-miR-3672	HITS-CLIP	23824327
MIRT639734	hsa-miR-3119	HITS-CLIP	23824327
MIRT639735	hsa-miR-873-3p	HITS-CLIP	23824327
MIRT639736	hsa-miR-3607-5p	HITS-CLIP	23824327
MIRT639737	hsa-miR-224-5p	HITS-CLIP	23824327
MIRT783529	hsa-miR-129-5p	HITS-CLIP	27418678
MIRT784375	hsa-miR-296-3p	HITS-CLIP	27418678
MIRT785179	hsa-miR-3674	HITS-CLIP	27418678
MIRT786561	hsa-miR-4732-5p	HITS-CLIP	27418678
MIRT789002	hsa-miR-6832-5p	HITS-CLIP	27418678

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000165	Process	MAPK cascade	TAS
GO:0000187	Process	Activation of MAPK activity	IBA	21873635
GO:0000187	Process	Activation of MAPK activity	TAS	19565474
GO:0004674	Function	Protein serine/threonine kinase activity	TAS
GO:0004708	Function	MAP kinase kinase activity	IBA	21873635
GO:0004708	Function	MAP kinase kinase activity	IDA	8388392
GO:0004712	Function	Protein serine/threonine/tyrosine kinase activity	TAS	19565474
GO:0004713	Function	Protein tyrosine kinase activity	IEA
GO:0005078	Function	MAP-kinase scaffold activity	IMP	29433126
GO:0005515	Function	Protein binding	IPI	11909642, 17979178, 21615688, 21988832, 24746704, 25416956, 25600339, 25852190, 27086506, 28514442, 29433126, 31980649, 32296183, 32814053
GO:0005524	Function	ATP binding	IEA
GO:0005576	Component	Extracellular region	NAS	8388392
GO:0005634	Component	Nucleus	TAS	19565474
GO:0005739	Component	Mitochondrion	TAS	19565474
GO:0005769	Component	Early endosome	TAS	19565474
GO:0005770	Component	Late endosome	TAS	19565474
GO:0005778	Component	Peroxisomal membrane	HDA	21525035
GO:0005783	Component	Endoplasmic reticulum	IDA	21615688
GO:0005794	Component	Golgi apparatus	IDA	21615688
GO:0005794	Component	Golgi apparatus	TAS	19565474
GO:0005829	Component	Cytosol	TAS	19565474
GO:0005874	Component	Microtubule	IDA	21615688
GO:0005911	Component	Cell-cell junction	IDA	21615688
GO:0005925	Component	Focal adhesion	TAS	19565474
GO:0009898	Component	Cytoplasmic side of plasma membrane	IDA	21615688
GO:0010629	Process	Negative regulation of gene expression	IGI	23626836
GO:0018108	Process	Peptidyl-tyrosine phosphorylation	IEA
GO:0030165	Function	PDZ domain binding	IDA	21615688
GO:0032872	Process	Regulation of stress-activated MAPK cascade	TAS	19565474
GO:0036289	Process	Peptidyl-serine autophosphorylation	IDA	8388392
GO:0043539	Function	Protein serine/threonine kinase activator activity	IDA	8388392
GO:0045893	Process	Positive regulation of transcription, DNA-templated	IMP	24375836
GO:0046872	Function	Metal ion binding	IEA
GO:0048471	Component	Perinuclear region of cytoplasm	IDA	21615688
GO:0070371	Process	ERK1 and ERK2 cascade	IMP	24375836
GO:0070371	Process	ERK1 and ERK2 cascade	TAS
GO:0071902	Process	Positive regulation of protein serine/threonine kinase activity	IDA	8388392
GO:0090170	Process	Regulation of Golgi inheritance	TAS	19565474
GO:0097110	Function	Scaffold protein binding	IPI	10409742, 21615688
GO:1903800	Process	Positive regulation of production of miRNAs involved in gene silencing by miRNA	IMP	24375836
GO:2000641	Process	Regulation of early endosome to late endosome transport	TAS	19565474

Other IDs

• MIM: 601263
• HGNC: 6842
• e!Ensembl: ENSG00000126934

Protein

• UniProt ID: P36507
• Protein name: Dual specificity mitogen-activated protein kinase kinase 2 (MAP kinase kinase 2) (MAPKK 2) (EC 2.7.12.2) (ERK activator kinase 2) (MAPK/ERK kinase 2) (MEK 2)
• Protein function: Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. Activates the ERK1 and ERK2 MAP kinases (By similarity). Activates BRAF in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF dimerization and BRAF activation (PubMed:29433126).
• PDB: 1S9I, 4H3Q
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00069	Pkinase	72 → 369	Protein kinase domain	Domain

• Sequence:

  MLARRKPVLPALTINPTIAEGPSPTSEGASEANLVDLQKKLEELELDEQQKKRLEAFLTQ
  KAKVGELKDDDFERISELGAGNGGVVTKVQHRPSGLIMARKLIHLEIKPAIRNQIIRELQ
  VLHECNSPYIVGFYGAFYSDGEISICMEHMDGGSLDQVLKEAKRIPEEILGKVSIAVLRG
  LAYLREKHQIMHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSMANSFVGTRSYMAPERLQ
  GTHYSVQSDIWSMGLSLVELAVGRYPIPPPDAKELEAIFGRPVVDGEEGEPHSISPRPRP
  PGRPVSGHGMDSRPAMAIFELLDYIVNEPPPKLPNGVFTPDFQEFVNKCLIKNPAERADL
  KMLTNHTFIKRSEVEEVDFAGWLCKTLRLNQPGTPTRTAV

• Sequence length: 400